Cytological diagnosis of lymphoepithelial carcinoma: Simple yet confusing.

Lymphoepithelial carcinoma (LEC) of salivary glands are rare tumours and present as gradually progressing painless masses. LECs have good prognosis and accurate differentiation from secondary tumours and nasopharyngeal carcinoma is essential to dictate management. We present a case of an elderly male presenting with a parotid swelling diagnosed as LEC on fine needle aspiration cytology and confirmed on histopathology and immunohistochemistry.

Melatonin-Loaded Nanoparticles Augment Mitophagy to Retard Parkinson's Disease.

The molecular pathways that melatonin follows as a Parkinson's disease (PD) antagonist remain poorly elucidated, despite it being a safe and a potential neurotherapeutic drug with a few limitations such as less bioavailability, premature oxidation, brain delivery, etc. Here, we used a biocompatible protein (HSA) nanocarrier for the delivery of melatonin to the brain. This nanomelatonin showed better antioxidative and neuroprotective properties, and it not only improves mitophagy to remove unhealthy mitochondria but also improves mitochondrial biogenesis to counteract rotenone-induced toxicity in an in vitro PD model. We also showed BMI1, a member of the PRC1 complex that regulates mitophagy, whose protein expression was enhanced after nanomelatonin dosage. These effects were translated to a rodent model, where nanomelatonin improves the TH+ve neuron population in SNPC and protects against rotenone-mediated toxicity. Our findings highlight the significantly better in vitro and in vivo neuroprotective effect of nanomelatonin as well as the molecular/cellular dynamics it influences to regulate mitophagy as a measure of the potential therapeutic candidate for PD.

Progress in gene editing tools, implications and success in plants: a review.

Genetic modifications are made through diverse mutagenesis techniques for crop improvement programs. Among these mutagenesis tools, the traditional methods involve chemical and radiation-induced mutagenesis, resulting in off-target and unintended mutations in the genome. However, recent advances have introduced site-directed nucleases (SDNs) for gene editing, significantly reducing off-target changes in the genome compared to induced mutagenesis and naturally occurring mutations in breeding populations. SDNs have revolutionized genetic engineering, enabling precise gene editing in recent decades. One widely used method, homology-directed repair (HDR), has been effective for accurate base substitution and gene alterations in some plant species. However, its application has been limited due to the inefficiency of HDR in plant cells and the prevalence of the error-prone repair pathway known as non-homologous end joining (NHEJ). The discovery of CRISPR-Cas has been a game-changer in this field. This system induces mutations by creating double-strand breaks (DSBs) in the genome and repairing them through associated repair pathways like NHEJ. As a result, the CRISPR-Cas system has been extensively used to transform plants for gene function analysis and to enhance desirable traits. Researchers have made significant progress in genetic engineering in recent years, particularly in understanding the CRISPR-Cas mechanism. This has led to various CRISPR-Cas variants, including CRISPR-Cas13, CRISPR interference, CRISPR activation, base editors, primes editors, and CRASPASE, a new CRISPR-Cas system for genetic engineering that cleaves proteins. Moreover, gene editing technologies like the prime editor and base editor approaches offer excellent opportunities for plant genome engineering. These cutting-edge tools have opened up new avenues for rapidly manipulating plant genomes. This review article provides a comprehensive overview of the current state of plant genetic engineering, focusing on recently developed tools for gene alteration and their potential applications in plant research.

A Novel Blockchain and Internet of Things-Based Food Traceability System for Smart Cities.

Rapid urbanization has recently caused serious problems for cities all around the world. Smart cities have drawn much interest from researchers in the present research paradigm to manage the expanding urban population. Frameworks for smart cities are planned and implemented using platforms based on blockchain and the Internet of Things (BIOT). Smart cities may use the BIoT platform to provide improved transportation, food traceability, and healthcare services. Food safety is one of the sectors where less research has been done than the others. The importance of food safety is now more widely recognized, making it essential to improve the traceability and transparency of the food supply chain. In this paper, a novel BIOT-based layered framework using EOSIO has been proposed for effective food traceability. The proposed system first identifies the suitable traceability units to provide better transparency and traceability and then defines and implements a layered architecture using Ethereum and EOSIO blockchain platforms. The performance of the proposed EOSIO-based model is evaluated using the practicality of the consensus algorithm, block production rate, throughput, and block confirmation time. The proposed traceability system attains a block production rate of 0.5 s and a block confirmation time of 1 s, which is much lower than the Ethereum-based traceability system. Hence, from the experimental evidence, the superiority of the proposed EOSIO-based food traceability can be observed.

Comprehensive spatio-temporal benchmarking of surface water quality of Hindon River, a tributary of river Yamuna, India: Adopting multivariate statistical approach.

The Hindon River is the main tributary of river Yamuna and it is a significant source of surface water, which flows through the major cities of western Uttar Pradesh, India. The indiscriminate development of industries and urbanization along river basin coupled with rapid population growths contribute various amounts of pollutant in the river. Therefore, the present study was conducted to assess the spatial-temporal variability of river water quality (seventeen physicochemical parameters and eight heavy metals) during pre- and post-monsoon seasons for 5 years data at 19 sampling sites along the river stretch. Indices associated with water quality and heavy metals were computed to scale the accurate state of risk associated to its use for drinking and irrigation. During the pre- and post-monsoon seasons, only four sites were found having safe water quality index (WQI) values. The mean heavy metal concentrations are found in order of Zn > Fe > Pb > Cu > Cr > Cd > Ni > Mn. Considering the spatial and temporal distribution, the study benchmarked the water quality of Hindon River for priority attention.

Expression Profiling of Four Mango FT/TFL1-Encoding Genes under Different Fruit Load Conditions, and Their Involvement in Flowering Regulation.

Plant flowering is antagonistically modulated by similar FLOWERING LOCUS T (FT) and TERMINAL FLOWER 1 (TFL1) proteins. In mango (Mangifera indica L.), flowering is induced by cold temperatures, unless the tree is juvenile or the adult tree had a high fruit load (HFL) in the summer. Here, we studied the effects of juvenility and fruit load on the expression of four MiFT/TFL1 genes cloned from the mango 'Shelly' cultivar. Ectopic expression of MiFT1 in Arabidopsis resulted in early flowering, whereas over-expression of MiFT2 and the two cloned MiTFL1 genes repressed flowering. Moreover, juvenility was positively correlated with higher transcript levels of MiFT2 and both MiTFL1s. In trees with a low fruit load, leaf MiFT1 expression increased in winter, whereas HFL delayed its upregulation. MiFT2 expression was upregulated in both leaves and buds under both fruit load conditions. Downregulation of both MITFL1s in buds was associated with a decrease in regional temperatures under both conditions; nevertheless, HFL delayed the decrease in their accumulation. Our results suggest that cold temperature has opposite effects on the expression of MiFT1 and the MiTFL1s, thereby inducing flowering, whereas HFL represses flowering by both suppressing MiFT1 upregulation and delaying MiTFL1s downregulation. The apparent flowering-inhibitory functions of MiFT2 are discussed.

Nanoemulsified Genistein and Vitamin D Mediated Epigenetic Regulation to Inhibit Osteoporosis.

The imbalance in the bone remodeling process with more bone resorption by osteoclasts compared to bone formation by osteoblasts results in a metabolic bone disorder known as osteoporosis. This condition reduces the bone mineral density and increases the risk of fractures due to low bone mass and disrupted bone microarchitecture. Osteoclastogenesis increases when the receptor activator NFκB ligand (RANKL) on the osteoblast surface binds to the receptor activator NFκB (RANK) on the osteoclast surface and the function of the decoy receptor of RANKL, osteoprotegrin, is compromised due to external stimuli such as heparin and lipopolysaccharides. The RANK/RANKL axis promotes the nuclear factor kappa B (NFκB) expression, which in turn increases the histone methyltransferase activity of EzH2 and EzH1 for the epigenetic regulation of osteoclastogenesis-related genes. Genistein counteracts NFκB-induced osteoclastogenesis and downstream signaling through the direct regulation of histone methyltransferase, EzH2 and EzH1, transcription. However, genistein possesses limitations like low bioavailability, low water solubility, high estrogen activity, and thyroid side effects, which obstruct its therapeutic usage. Here, the nanoemulsified formulation of genistein with vitamin D was utilized to circumvent the limitations of genistein so that it can be utilized for therapeutic purposes in osteoporosis management. The nanoemulsification of genistein and vitamin D was performed through the spontaneous emulsification using Tween 80 and medium chain triglyceride oil as an organic phase. The physiologically stable and biocompatible combination of the genistein and vitamin D nanoemulsion (GVNE) exhibited the controlled release pattern of genistein with Korsmeyer-Peppas and Higuchi models under different pH conditions (7.4, 6.5, and 1.2). The GVNE potentially enhanced the therapeutic efficacy under in vitro osteoporosis models and helped restore disease parameters like alkaline phosphatase activity, tartrate-resistant acid phosphatase activity, and the formation of multinuclear giant cells. Molecularly, the GVNE overturned the LPS-induced osteoclastogenesis by downregulation of NFκB expression along with its binding on EzH2 and EzH1 promoters. GVNE effects on the osteoporosis model established it as an efficient antiosteoporotic therapy. This nanonutraceutical-based formulation provides an epigenetic regulation of osteoporosis management and opens new avenues for alternate epigenetic therapies for osteoporosis.

Melatonin mediated inhibition of EZH2-NOS2 crosstalk attenuates inflammatory bowel disease in preclinical in vitro and in vivo models.

AIMS: Inflammatory Bowel Disease is characterised by abdominal pain, diarrhoea, rectal bleeding and weight loss. Sometimes it may leads to severe health complications resulting in death of an individual. Current research efforts to highlight the role of melatonin in regulating EZH2, a master epigenetic regulator and its beneficiary effect in case of IBD management. MATERIAL METHODS: Murine macrophages (RAW 264.7) were treated with lipopolysaccharides (LPS) to activate them for generating inflammatory response to investigate efficacy of melatonin in-vitro models. Similarly, for developing in vivo models, Dextran sodium sulphate (36-50 kDa) was used. Evaluations of anti-inflammatory activities were carried out by nitrite assay, western blotting, q-PCR, immunofluorescence, and histological studies. KEY FINDINGS: Reduction of epigenetic target, EZH2 by melatonin significantly improves the clinical symptoms of dextran sodium sulphate induced colitis and may be implicated as a potential therapeutic target in IBD management. The present study evaluates the efficacy of melatonin by epigenetic regulation in IBD models. Down regulation of EZH2 by melatonin reduced the chemical induced inflammatory insults in in vitro and in vivo models. Exploration of molecular pathways has revealed interlink of EZH2 and NOS2, a hallmark of inflammation. Molecular mechanistic action of melatonin is attributed to inhibition of the expression and physical interaction of EZH2 and NOS2. SIGNIFICANCE: Our study highlights melatonin therapeutic effect via attenuating interaction between EZH2 and NOS2 which is beneficial in managing IBD treatment.

A comprehensive survey of image segmentation: clustering methods, performance parameters, and benchmark datasets.

Image segmentation is an essential phase of computer vision in which useful information is extracted from an image that can range from finding objects while moving across a room to detect abnormalities in a medical image. As image pixels are generally unlabelled, the commonly used approach for the same is clustering. This paper reviews various existing clustering based image segmentation methods. Two main clustering methods have been surveyed, namely hierarchical and partitional based clustering methods. As partitional clustering is computationally better, further study is done in the perspective of methods belonging to this class. Further, literature bifurcates the partitional based clustering methods into three categories, namely K-means based methods, histogram-based methods, and meta-heuristic based methods. The survey of various performance parameters for the quantitative evaluation of segmentation results is also included. Further, the publicly available benchmark datasets for image-segmentation are briefed.

Potential Anti-Mycobacterium tuberculosis Activity of Plant Secondary Metabolites: Insight with Molecular Docking Interactions.

Tuberculosis (TB) is a recurrent and progressive disease, with high mortality rates worldwide. The drug-resistance phenomenon of Mycobacterium tuberculosis is a major obstruction of allelopathy treatment. An adverse side effect of allelopathic treatment is that it causes serious health complications. The search for suitable alternatives of conventional regimens is needed, i.e., by considering medicinal plant secondary metabolites to explore anti-TB drugs, targeting the action site of M. tuberculosis. Nowadays, plant-derived secondary metabolites are widely known for their beneficial uses, i.e., as antioxidants, antimicrobial agents, and in the treatment of a wide range of chronic human diseases (e.g., tuberculosis), and are known to "thwart" disease virulence. In this regard, in silico studies can reveal the inhibitory potential of plant-derived secondary metabolites against Mycobacterium at the very early stage of infection. Computational approaches based on different algorithms could play a significant role in screening plant metabolites against disease virulence of tuberculosis for drug designing.

A new clustering method for the diagnosis of CoVID19 using medical images.

With the spread of COVID-19, there is an urgent need for a fast and reliable diagnostic aid. For the same, literature has witnessed that medical imaging plays a vital role, and tools using supervised methods have promising results. However, the limited size of medical images for diagnosis of CoVID19 may impact the generalization of such supervised methods. To alleviate this, a new clustering method is presented. In this method, a novel variant of a gravitational search algorithm is employed for obtaining optimal clusters. To validate the performance of the proposed variant, a comparative analysis among recent metaheuristic algorithms is conducted. The experimental study includes two sets of benchmark functions, namely standard functions and CEC2013 functions, belonging to different categories such as unimodal, multimodal, and unconstrained optimization functions. The performance comparison is evaluated and statistically validated in terms of mean fitness value, Friedman test, and box-plot. Further, the presented clustering method tested against three different types of publicly available CoVID19 medical images, namely X-ray, CT scan, and Ultrasound images. Experiments demonstrate that the proposed method is comparatively outperforming in terms of accuracy, precision, sensitivity, specificity, and F1-score.

Formulation and performance evaluation of polymeric mixed micelles encapsulated with baicalein for breast cancer treatment.

The present study is aimed to formulate baicalein-loaded mixed micelles to enhance the solubility and oral bioavailability. Baicalein encapsulated D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and pluronic F127 (F127) combined micelles were prepared and investigated for anticancer effect. The optimized formulation contains 25.04 ± 0.24 nm mean particle size of micelles with a zeta potential value of -4.01 ± 0.5 mV. The calculated entrapment efficiency percentage of baicalein within the micellar structure was 83.43 ± 0.13% and the in vitro release of baicalein from micelles displayed a sustained release profile at pH 7.4. The incorporation of baicalein within micelles core was also confirmed by FTIR analysis of formulation, which hardly represents the characteristic peak of baicalein, indicating successful entrapment of the drug. In vitro cell culture experiments revealed baicalein-loaded micelles significantly enhanced cellular uptake and cytotoxicity against MDAMB-231 cell lines in comparison to free baicalein. Additionally, as compared to free baicalein, baicalein micelles demonstrated greater apoptosis-inducing potential while the results of the cell cycle study exhibited arrest of cells at the G0/G1 phase of the cell cycle. Results of ROS (reactive oxygen species) and MMP (mitochondrial membrane potential) assay revealed the ROS-dependent mitochondrial-mediated apoptosis pathway utilized by developed formulation to inhibit cell proliferation. Thus, the developed nano micelles can serve as a potent carrier system for baicalein against breast cancer.

Modified plant architecture integrated with liquid fertilizers improves fruit productivity and quality of tomato in North West Himalaya, India.

India produces around 19.0 million tonnes of tomatoes annually, which is insufficient to meet the ever-increasing demand. A big gap of tomato productivity (72.14 t ha-1) between India (24.66 t ha-1) and the USA (96.8 t ha-1) exist, which can be bridged by integrating trellis system of shoot training, shoot pruning, liquid fertilizers, farmyard manure, and mulching technologies. Therefore, the present experiment was conducted on tomato (cv. Himsona) during 2019-2020 at farmers' fields to improve tomato productivity and quality. There were five treatments laid in a randomized block design (RBD) with three replications; T1 [Farmer practice on the flatbed with RDF @ N120:P60:K60 + FYM @6.0 t ha-1 without mulch], T2 [T1 + Polythene mulch (50 microns)], T3 [Tomato plants grown on the raised bed with polythene mulch + FYM @ 8.0 t ha-1 + Single shoot trellis system + Side shoot pruning + Liquid Fertilizer (LF1-N19:P19:K19) @ 2.0 g l-1 for vegetative growth + Liquid Fertilizer (LF2-N0: P52: K34) @ 1.5 g l-1 for improving fruit quality], T4 [Tomato plants grown on the raised bed with polythene mulch + FYM @ 8.0 t ha-1 + Single shoot trellis system + Side shoot pruning + LF1 @ 4.0 g l-1 + LF2 @ 3.0 g l-1], and T5 [Tomato plants grown on the raised bed with polythene mulch + FYM @ 10.0 t ha-1 + Single shoot trellis system + Side shoot pruning + LF1 @ 6.0 g l-1 + LF2 @ 4.5 g l-1]. The results revealed that tomato plant grown on the raised beds with polythene mulch, shoot pruning, trellising, liquid fertilizers, and farmyard manure (i.e., T5) recorded higher shoot length, dry matter content, and tomato productivity by 20.75-141.21, 18.79-169.4, and 18.89-160.87% as compared to T4-T1 treatments, respectively. The T5 treatment also recorded the highest water productivity (28.39 kg m-3), improved fruit qualities, net return (10,751 USD ha-1), benefit-cost ratio (3.08), microbial population, and enzymatic activities as compared to other treatments. The ranking and hierarchical clustering of treatments confirmed the superiority of the T5 treatment over all other treatments.

Engineered BcZAT12 gene mitigates salt stress in tomato seedlings.

In salt-prone areas, plant growth and productivity is adversely affected. In the present study, the ZT1-ZT6 transgenic tomato lines having BcZAT12 gene under the regulatory control of the stress inducible Bclea1 promoter were exposed to three salinity levels (50, 100 and 200 mM) at the four leaf stage for 10 days. The transgenic lines showed improved growth in stem height, leaf area, root length and shoot length under saline conditions, as compared to control. Moreover, ZT1 and ZT5 lines showed lower electrolyte leakage and decreased hydrogen peroxide formation, in combination with elevated relative water content, proline and chlorophyll levels. The enzyme activity of catalase was also enhanced in ZT1 and ZT5. These results poses the present lines as an attractive alternative for tomato cultivation in salinity-affected areas.

Characterization of Two Ethephon-Induced IDA-Like Genes from Mango, and Elucidation of Their Involvement in Regulating Organ Abscission.

In mango (Mangifera indica L.), fruitlet abscission limits productivity. The INFLORESCENCE DEFICIENT IN ABSCISSION (IDA) peptide acts as a key component controlling abscission events in Arabidopsis. IDA-like peptides may assume similar roles in fruit trees. In this study, we isolated two mango IDA-like encoding-genes, MiIDA1 and MiIDA2. We used mango fruitlet-bearing explants and fruitlet-bearing trees, in which fruitlets abscission was induced using ethephon. We monitored the expression profiles of the two MiIDA-like genes in control and treated fruitlet abscission zones (AZs). In both systems, qRT-PCR showed that, within 24 h, both MiIDA-like genes were induced by ethephon, and that changes in their expression profiles were associated with upregulation of different ethylene signaling-related and cell-wall modifying genes. Furthermore, ectopic expression of both genes in Arabidopsis promoted floral-organ abscission, and was accompanied by an early increase in the cytosolic pH of floral AZ cells-a phenomenon known to be linked with abscission, and by activation of cell separation in vestigial AZs. Finally, overexpression of both genes in an Atida mutant restored its abscission ability. Our results suggest roles for MiIDA1 and MiIDA2 in affecting mango fruitlet abscission. Based on our results, we propose new possible modes of action for IDA-like proteins in regulating organ abscission.

Drug Resistance Reversal Potential of Nanoparticles/Nanocomposites via Antibiotic's Potentiation in Multi Drug Resistant P. aeruginosa.

Bacteria employ numerous resistance mechanisms against structurally distinct drugs by the process of multidrug resistance. A study was planned to discover the antibacterial potential of a graphene oxide nanosheet (GO), a graphene oxide-zinc oxide nanocomposite (GO/ZnO), a graphene oxide-chitosan nanocomposite (GO-CS), a zinc oxide decorated graphene oxide-chitosan nanocomposite (GO-CS/ZnO), and zinc oxide nanoparticles (ZnO) alone and in a blend with antibiotics against a PS-2 isolate of Pseudomonas aeruginosa. These nanocomposites reduced the MIC of tetracycline (TET) from 16 folds to 64 folds against a multidrug-resistant clinical isolate. Efflux pumps were interfered, as evident by an ethidium bromide synergy study with nanocomposites, as well as inhibiting biofilm synthesis. These nanoparticles/nanocomposites also decreased the mutant prevention concentration (MPC) of TET. To the best of our knowledge, this is the first report on nanomaterials as a synergistic agent via inhibition of efflux and biofilm synthesis.

Genistein nanoformulation promotes selective apoptosis in oral squamous cell carcinoma through repression of 3PK-EZH2 signalling pathway.

BACKGROUND: Overexpression of polycomb protein contributes to epigenetic repression in oral squamous cell carcinoma (OSCC) ensuing in poor prognosis and aggressive phenotype. Several plant-based compounds could help prevent epigenome alteration and cancer progression, but their low bioavailability limits their therapeutic activity. HYPOTHESIS: In this study, we have synthesized genistein nanoformulation (GLNPs) and evaluated its epigenetic regulation mechanism for selective apoptosis induction in OSCC. METHODS: Lactalbumin was used to prepare nanoformulation of Genistein. The mechanism of epigenetic regulation and selective apoptosis by Genistein loaded nanoparticles was studied in OSCC cell line JHU011 and fibroblast cell line L929 using immunofluorescence, Western blotting and ChIP-qPCR assay. RESULTS: We have found that GLNPs treatment selectively induced apoptosis in OSCC compared to the normal fibroblast cells. This selective effect in OSCC is achieved through enhanced reactive oxygen species (ROS) generation followed by Bax mitochondrial translocation and caspase 3 activation. Further, GLNPs induced withdrawal of epigenetic transcription repression through concurrent downregulation of the polycomb group proteins (PcG) Bmi 1 and EZH2 along with their successive targets, UbH2AK119 and H3K27me3, which have immense therapeutic implications in the treatment of OSCC. Last, we have established that GLNPs regulate EZH2expression through proteasomal mediated degradation and 3PK inhibition; 3PK protein was found physically linked with EZH2 protein and its promoter region (-1107 to -1002). This event indicates that 3PK might play some crucial role in EZH2 expression and epigenetic control of OSCC. Moreover, the formulation showed improved biodistribution, aqueous dispersibility and enhanced biocompatibility In-vivo. CONCLUSIONS: These results provide evidence that GLNPs may withdraw epigenetic transcriptional repression and selectively induce apoptosis in human oral squamous cell carcinoma.

Prevalence of Sleep Disturbances During COVID-19 Pandemic in a Nepalese Population: A Cross-Sectional Study

Objectives@#The coronavirus disease (COVID-19) pandemic and news of daily increasing cases inside Nepal and worldwide is adding to the fear that leads to anger, anxiety, frustration, and stress, emotions that directly affect sleep quality. This study aimed to assess sleep disturbances during the COVID-19 pandemic in a Nepalese population. @*Methods@#This cross-sectional study recruited 206 Nepali residents who completed anonymous self-administered questionnaires. The Insomnia Severity Index (ISI) questionnaire was used to measure sleep disturbances before and after the COVID-19 pandemic. The gathered data were analyzed using descriptive statistics and inferential statistics using SPSS version 20 statistical software. @*Results@#There was a significant variation in sleep disturbances among Nepalese residents before versus after the COVID-19 pandemic (p<0.001). The prevalence of clinical moderate insomnia has increased tremendously in Nepalese individuals. Before the pandemic’s onset, only 3.9% of the participants had moderate to severe levels of clinical insomnia; after its onset, this value increased to 17.5%. The mean ISI scores were 6.35±4.65 and 8.01±6.01 before and after the pandemic’s onset, respectively. @*Conclusions@#Our study findings suggest that people are suffering tremendously with sleep disturbances and calls for further research and active measures to help increase sleep quality during the COVID-19 pandemic.

A non-viral nano-delivery system targeting epigenetic methyltransferase EZH2 for precise acute myeloid leukemia therapy.

Acute myeloid leukemia (AML), which is common in the elderly population, accounts for poor long-term survival with a high possibility of relapse. The associated lack of currently developed therapeutics is directing the search for new therapeutic targets relating to AML. EZH2 (Enhancer of Zeste Homolog 2) is a histone methyltransferase member of the polycomb-group (PcG) family, and its significant overexpression in AML means it has emerged as a potential epigenetic target. Here, we propose the human serum albumin (HSA) nanoparticle based delivery of small interfering RNA (siRNA), which can target EZH2-expressing genes in AML. EZH2 specific siRNA loaded in a polyethyleneimine (PEI) conjugated HSA nanocarrier can overcome the systemic instability of siRNA and precisely target the AML cell population for increased EZH2 gene silencing. A stable nanosized complex (HSANPs-PEI@EZH2siRNA), achieved via the electrostatic interaction of PEI and EZH2 siRNA, shows increased systemic stability and hemocompatibility, and enhanced EZH2 gene silencing activity in vitro, compared to conventional transfection reagents. HSANPs-PEI@EZH2siRNA-treated AML cells showed downregulated EZH2, which is associated with a reduced level of Bmi-1 protein, and H3K27me3 and H2AK119ub modification. The ubiquitin-mediated proteasomal degradation pathway plays a critical role in the downregulation of associated proteins following HSANPs-PEI@EZH2siRNA exposure to AML cells. c-Myb is the AML-responsive transcription factor that directly binds on the EZH2 promoter and was downregulated in HSANPs-PEI@EZH2siRNA-treated AML cells. The systemic exposure to HSANPs-PEI@EZH2siRNA of AML engrafted immunodeficient nude mice displayed efficient EZH2 gene silencing and a reduced AML cell population in peripheral blood and bone marrow. The present study demonstrates a non-viral siRNA delivery system for epigenetic targeting based superior anti-leukemic therapy.